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Published in: BMC Cancer 1/2008

Open Access 01-12-2008 | Research article

Improved therapeutic effectiveness by combining liposomal honokiol with cisplatin in lung cancer model

Authors: Qi-qi Jiang, Lin-yu Fan, Guang-li Yang, Wen-Hao Guo, Wen-li Hou, Li-juan Chen, Yu-quan Wei

Published in: BMC Cancer | Issue 1/2008

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Abstract

Background

Honokiol is a major bioactive compound extracted from Magnolia. The present study was designed to determine whether liposomal honokiol has the antitumor activity against human lung cancer as well as potentiates the antitumor activity of cisplatin in A549 lung cancer xenograft model, if so, to examine the possible mechanism in the phenomenon.

Methods

human A549 lung cancer-bearing nude mice were treated with liposomal honokiol, liposomal honokiol plus DDP or with control groups. Apoptotic cells and vessels were evaluated by fluorescent in situ TUNEL assay and by immunohistochemistry with an antibody reactive to CD31 respectively.

Results

The present study showed that liposomal honokiol alone resulted in effective suppression of the tumor growth, and that the combined treatment with honokiol plus DDP had the enhanced inhibition of the tumor growth and resulted in a significant increase in life span. The more apparent apoptotic cells in the tumors treated with honokiol plus DDP was found in fluorescent in situ TUNEL assay, compared with the treatment with control groups. In addition, the combination of honokiol and DDP apparently reduced the number of vessels by immunolabeling of CD31 in the tissue sections, compared with control groups.

Conclusion

In summary, our data suggest that honokiol alone had the antitumor activity against human lung cancer in A549 lung cancer xenograft model, and that the combination of honokiol with DDP can enhance the antitumor activity, and that the enhanced antitumor efficacy in vivo may in part result from the increased induction of the apoptosis and the enhanced inhibition of angiogenesis in the combined treatment. The present findings may be of importance to the further exploration of the potential application of the honokiol alone or the combined approach in the treatment of lung carcinoma.
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Literature
1.
go back to reference Khuri FR, Herbst RS, Fossella FV: Emerging therapies in non-small-cell lung cancer. Ann Oncol. 2001, 12: 739-44. 10.1023/A:1011197500223.CrossRefPubMed Khuri FR, Herbst RS, Fossella FV: Emerging therapies in non-small-cell lung cancer. Ann Oncol. 2001, 12: 739-44. 10.1023/A:1011197500223.CrossRefPubMed
2.
go back to reference Soria J-C, Jiang SJ, Khuri FR, Hassan K, Liu D, Hong WK, Mao L: Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its clinical implication. Cancer Res. 2000, 60: 4000-4.PubMed Soria J-C, Jiang SJ, Khuri FR, Hassan K, Liu D, Hong WK, Mao L: Overexpression of cyclin B1 in early-stage non-small cell lung cancer and its clinical implication. Cancer Res. 2000, 60: 4000-4.PubMed
3.
go back to reference Vora SA, Daly BDT, Blaszkowsky L, McGrath JJ, Bankoff M, Supran S, Dipetrillo TA: High dose radiation therapy and chemotherapy as induction treatment for stage III nonsmall cell lung carcinoma. Cancer. 2000, 89: 1946-52. 10.1002/1097-0142(20001101)89:9<1946::AID-CNCR10>3.0.CO;2-1.CrossRefPubMed Vora SA, Daly BDT, Blaszkowsky L, McGrath JJ, Bankoff M, Supran S, Dipetrillo TA: High dose radiation therapy and chemotherapy as induction treatment for stage III nonsmall cell lung carcinoma. Cancer. 2000, 89: 1946-52. 10.1002/1097-0142(20001101)89:9<1946::AID-CNCR10>3.0.CO;2-1.CrossRefPubMed
4.
go back to reference Bai X, Cerimele F, Ushio-Fukai M, Waqas M, Campbell PM, Govindarajan B, Der CJ, Battle T, Frank DA, Ye K, Murad E, Dubiel W, Soff G, Arbiser JkL: Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J Biol Chem. 2003, 278: 35501-7. 10.1074/jbc.M302967200.CrossRefPubMed Bai X, Cerimele F, Ushio-Fukai M, Waqas M, Campbell PM, Govindarajan B, Der CJ, Battle T, Frank DA, Ye K, Murad E, Dubiel W, Soff G, Arbiser JkL: Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J Biol Chem. 2003, 278: 35501-7. 10.1074/jbc.M302967200.CrossRefPubMed
5.
go back to reference Hirano T, Gotoh M, Oka K: Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells. Life Sci. 1994, 55: 1061-1069. 10.1016/0024-3205(94)00641-5.CrossRefPubMed Hirano T, Gotoh M, Oka K: Natural flavonoids and lignans are potent cytostatic agents against human leukemic HL-60 cells. Life Sci. 1994, 55: 1061-1069. 10.1016/0024-3205(94)00641-5.CrossRefPubMed
6.
go back to reference Wang T, Chen F, Chen Z, Wu YF, Xu XL, Zheng S, Hu X: Honokiol induces apoptosis through p53-independent pathway in human colorectal cell line RKO. World J Gastroenterol. 2004, 10: 2205-2208.PubMedPubMedCentral Wang T, Chen F, Chen Z, Wu YF, Xu XL, Zheng S, Hu X: Honokiol induces apoptosis through p53-independent pathway in human colorectal cell line RKO. World J Gastroenterol. 2004, 10: 2205-2208.PubMedPubMedCentral
7.
go back to reference Hibasami H, Achiwa Y, Katsuzaki H, Imai K, Yoshioka K, Nakanishi K, Ishii Y, Hasegawa M, Komiya T: Honokiol induces apoptosis in human lymphoid leukemia Molt 4B cells. Int J Mol Med. 1998, 2: 671-673.PubMed Hibasami H, Achiwa Y, Katsuzaki H, Imai K, Yoshioka K, Nakanishi K, Ishii Y, Hasegawa M, Komiya T: Honokiol induces apoptosis in human lymphoid leukemia Molt 4B cells. Int J Mol Med. 1998, 2: 671-673.PubMed
8.
go back to reference Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Hideshima H, Shiraishi N, Yasui H, Roccaro AM, Richardson P, Podar K, Gouill SL, Chauhan D, Tamura K, Arbiser J, Anderson KC: Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and independent apoptosis. Blood. 2005, 106: 1794-800. 10.1182/blood-2005-01-0346.CrossRefPubMedPubMedCentral Ishitsuka K, Hideshima T, Hamasaki M, Raje N, Kumar S, Hideshima H, Shiraishi N, Yasui H, Roccaro AM, Richardson P, Podar K, Gouill SL, Chauhan D, Tamura K, Arbiser J, Anderson KC: Honokiol overcomes conventional drug resistance in human multiple myeloma by induction of caspase-dependent and independent apoptosis. Blood. 2005, 106: 1794-800. 10.1182/blood-2005-01-0346.CrossRefPubMedPubMedCentral
9.
go back to reference Yang SE, Hsieh MT, Tsai TH, Hsu SL: Down-modulation of Bcl-XL, release of cytochrome c and sequential activation of caspases during honokiol-induced apoptosis in human squamous lung cancer CH27 cells. Biochem Pharmacol. 2002, 63: 1641-1651. 10.1016/S0006-2952(02)00894-8.CrossRefPubMed Yang SE, Hsieh MT, Tsai TH, Hsu SL: Down-modulation of Bcl-XL, release of cytochrome c and sequential activation of caspases during honokiol-induced apoptosis in human squamous lung cancer CH27 cells. Biochem Pharmacol. 2002, 63: 1641-1651. 10.1016/S0006-2952(02)00894-8.CrossRefPubMed
10.
go back to reference Konoshima T, Kozuka M, Tokuda H, Nishino H, Iwashima A, Haruna M, Ito K, Tanabe M: Studies on inhibitors of skin tumor promotion, IX: neolignans from Magnolia officinalis. J Nat Prod. 1991, 54: 816-822. 10.1021/np50075a010.CrossRefPubMed Konoshima T, Kozuka M, Tokuda H, Nishino H, Iwashima A, Haruna M, Ito K, Tanabe M: Studies on inhibitors of skin tumor promotion, IX: neolignans from Magnolia officinalis. J Nat Prod. 1991, 54: 816-822. 10.1021/np50075a010.CrossRefPubMed
11.
go back to reference The International Adjuvant Lung Cancer Trial Collaborative Group: Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004, 350: 351-60. 10.1056/NEJMoa031644.CrossRef The International Adjuvant Lung Cancer Trial Collaborative Group: Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer. N Engl J Med. 2004, 350: 351-60. 10.1056/NEJMoa031644.CrossRef
12.
go back to reference Folkman J: Seminars in medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med. 1995, 333: 1757-63. 10.1056/NEJM199512283332608.CrossRefPubMed Folkman J: Seminars in medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med. 1995, 333: 1757-63. 10.1056/NEJM199512283332608.CrossRefPubMed
13.
go back to reference Li G, Tian L, Hou JM, Ding ZY, He QM, Feng P, Jun WY, Xiao F, Yao B, Zhang R, Peng F, Jiang Y, Luo F, Zhao X, Zhang L, Zhou Q, Wei YQ: Improved therapeutic effectiveness by combining recombinant CXC chemokine ligand 10 with Cisplatin in solid tumors. Clin Cancer Res. 2005, 11: 4217-24. 10.1158/1078-0432.CCR-04-2117.CrossRefPubMed Li G, Tian L, Hou JM, Ding ZY, He QM, Feng P, Jun WY, Xiao F, Yao B, Zhang R, Peng F, Jiang Y, Luo F, Zhao X, Zhang L, Zhou Q, Wei YQ: Improved therapeutic effectiveness by combining recombinant CXC chemokine ligand 10 with Cisplatin in solid tumors. Clin Cancer Res. 2005, 11: 4217-24. 10.1158/1078-0432.CCR-04-2117.CrossRefPubMed
14.
go back to reference Wang X, Wang Y, Geng Y, Li F, Zheng C: Isolation and purification of honokiol and magnolol from cortex Magnoliae officinalis by high-speed counter-current chromatography. J Chromatogr A. 2004, 1036: 171-5. 10.1016/j.chroma.2004.02.073.CrossRefPubMed Wang X, Wang Y, Geng Y, Li F, Zheng C: Isolation and purification of honokiol and magnolol from cortex Magnoliae officinalis by high-speed counter-current chromatography. J Chromatogr A. 2004, 1036: 171-5. 10.1016/j.chroma.2004.02.073.CrossRefPubMed
15.
go back to reference Yuan ZP, Chen LJ, Fan LY, Tang MH, Yang GL, Yang HS, Du XB, Wang GQ, Yao WX, Zhao QM, Bin Y, Rui W, Peng D, Wei Z, Wu HB, Xia Z, Wei YQ: Liposomal quercetin efficiently suppresses growth of solid tumors in murine models. Clin Cancer Res. 2006, 12: 3193-9. 10.1158/1078-0432.CCR-05-2365.CrossRefPubMed Yuan ZP, Chen LJ, Fan LY, Tang MH, Yang GL, Yang HS, Du XB, Wang GQ, Yao WX, Zhao QM, Bin Y, Rui W, Peng D, Wei Z, Wu HB, Xia Z, Wei YQ: Liposomal quercetin efficiently suppresses growth of solid tumors in murine models. Clin Cancer Res. 2006, 12: 3193-9. 10.1158/1078-0432.CCR-05-2365.CrossRefPubMed
16.
go back to reference Saris CP, Vaart van de PJ, Rietbroek RC, Blommaert FA: In vitro formation of DNA adducts by cisplatin, lobaplatin and oxaliplatin in calf thymus DNA in solution and in cultured human cells. Carcinogenesis. 1996, 17: 2763-9. 10.1093/carcin/17.12.2763.CrossRefPubMed Saris CP, Vaart van de PJ, Rietbroek RC, Blommaert FA: In vitro formation of DNA adducts by cisplatin, lobaplatin and oxaliplatin in calf thymus DNA in solution and in cultured human cells. Carcinogenesis. 1996, 17: 2763-9. 10.1093/carcin/17.12.2763.CrossRefPubMed
17.
go back to reference Faivre S, Chan D, Salinas R, Woynarowska B, Woynarowski JM: DNA strand breaks and apoptosis induced by oxaliplatin in cancer cells. Biochem Pharmacol. 2003, 66: 225-37. 10.1016/S0006-2952(03)00260-0.CrossRefPubMed Faivre S, Chan D, Salinas R, Woynarowska B, Woynarowski JM: DNA strand breaks and apoptosis induced by oxaliplatin in cancer cells. Biochem Pharmacol. 2003, 66: 225-37. 10.1016/S0006-2952(03)00260-0.CrossRefPubMed
18.
go back to reference Zhong X, Li X, Wang G, Zhu Y, Hu G, Zhao J, Neace C, Ding H, Reed E, Li QQ: Mechanisms underlying the synergistic effect of SU5416 and cisplatin on cytotoxicity in human ovarian tumor cells. Int J Oncol. 2004, 25: 445-51.PubMed Zhong X, Li X, Wang G, Zhu Y, Hu G, Zhao J, Neace C, Ding H, Reed E, Li QQ: Mechanisms underlying the synergistic effect of SU5416 and cisplatin on cytotoxicity in human ovarian tumor cells. Int J Oncol. 2004, 25: 445-51.PubMed
19.
go back to reference Yoshikawa A, Saura R, Matsubara T, Mizuno K: A mechanism of cisplatin action: antineoplastic effect through inhibition of neovascularization. Kobe J Med Sci. 43: 109-120. Yoshikawa A, Saura R, Matsubara T, Mizuno K: A mechanism of cisplatin action: antineoplastic effect through inhibition of neovascularization. Kobe J Med Sci. 43: 109-120.
20.
go back to reference Ahn KS, Sethi G, Shishodia S, Sung B, Arbiser JL, Aggarwal BB: Honokiol potentiates apoptosis, suppresses osteoclastogenesis, and inhibits invasion through modulation of nuclear factor-kappaB activation pathway. Mol Cancer Res. 2006, 4: 621-33. 10.1158/1541-7786.MCR-06-0076.CrossRefPubMed Ahn KS, Sethi G, Shishodia S, Sung B, Arbiser JL, Aggarwal BB: Honokiol potentiates apoptosis, suppresses osteoclastogenesis, and inhibits invasion through modulation of nuclear factor-kappaB activation pathway. Mol Cancer Res. 2006, 4: 621-33. 10.1158/1541-7786.MCR-06-0076.CrossRefPubMed
21.
go back to reference Shigemura K, Arbiser JL, Sun SY, Zayzafoon M, Johnstone PA, Fujisawa M, Gotoh A, Weksler B, Zhau HE, Chung LW: Honokiol, a natural plant product, inhibits the bone metastatic growth of human prostate cancer cells. Cancer. 2007, 109: 1279-89. 10.1002/cncr.22551.CrossRefPubMed Shigemura K, Arbiser JL, Sun SY, Zayzafoon M, Johnstone PA, Fujisawa M, Gotoh A, Weksler B, Zhau HE, Chung LW: Honokiol, a natural plant product, inhibits the bone metastatic growth of human prostate cancer cells. Cancer. 2007, 109: 1279-89. 10.1002/cncr.22551.CrossRefPubMed
22.
go back to reference Battle TE, Arbiser J, Frank DA: The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Blood. 2005, 106: 690-697. 10.1182/blood-2004-11-4273.CrossRefPubMed Battle TE, Arbiser J, Frank DA: The natural product honokiol induces caspase-dependent apoptosis in B-cell chronic lymphocytic leukemia (B-CLL) cells. Blood. 2005, 106: 690-697. 10.1182/blood-2004-11-4273.CrossRefPubMed
23.
go back to reference Klement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ: Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest. 2000, 105: 15-24. 10.1172/JCI8829.CrossRef Klement G, Baruchel S, Rak J, Man S, Clark K, Hicklin DJ: Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest. 2000, 105: 15-24. 10.1172/JCI8829.CrossRef
24.
go back to reference Williams JI, Weitman S, Gonzalez CM, Jundt CH, Marty J, Stringer SD, Holroyd KJ, Mclane MP, Qiming C, Zasloff M, Von HD: Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies. Clin Cancer Res. 2001, 7: 724-33.PubMed Williams JI, Weitman S, Gonzalez CM, Jundt CH, Marty J, Stringer SD, Holroyd KJ, Mclane MP, Qiming C, Zasloff M, Von HD: Squalamine treatment of human tumors in nu/nu mice enhances platinum-based chemotherapies. Clin Cancer Res. 2001, 7: 724-33.PubMed
25.
go back to reference Aoyama Y, Avruch J, Zhang XF: Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases. Oncogene. 2004, 23: 3426-33. 10.1038/sj.onc.1207486.CrossRefPubMed Aoyama Y, Avruch J, Zhang XF: Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases. Oncogene. 2004, 23: 3426-33. 10.1038/sj.onc.1207486.CrossRefPubMed
26.
go back to reference Viloria-Petit AM, Kerbel RS: Acquired resistance to EGFR inhibitors: mechanisms and prevention strategies. Int J Radiat Oncol Biol Phys. 2004, 58 (3): 914-926.CrossRefPubMed Viloria-Petit AM, Kerbel RS: Acquired resistance to EGFR inhibitors: mechanisms and prevention strategies. Int J Radiat Oncol Biol Phys. 2004, 58 (3): 914-926.CrossRefPubMed
27.
go back to reference Muther RS, Bennett WM: Ejects of dimethyl sulfoxide on renal function in man. JAMA. 1980, 244: 2081-3. 10.1001/jama.244.18.2081.CrossRefPubMed Muther RS, Bennett WM: Ejects of dimethyl sulfoxide on renal function in man. JAMA. 1980, 244: 2081-3. 10.1001/jama.244.18.2081.CrossRefPubMed
28.
go back to reference Marshall LF, Camp PE, Bowers SA: Dimethyl sulfoxide for the treatment of intracranial hypertension: a preliminary trial. Neurosurgery. 1984, 14: 659-63. 10.1097/00006123-198406000-00002.CrossRefPubMed Marshall LF, Camp PE, Bowers SA: Dimethyl sulfoxide for the treatment of intracranial hypertension: a preliminary trial. Neurosurgery. 1984, 14: 659-63. 10.1097/00006123-198406000-00002.CrossRefPubMed
29.
go back to reference Rijtema M, Mosig D, Drukker A, Guignard JP: The effects of dimethyl sulfoxide on renal function of the newborn rabbit. Biol Neonate. 1999, 76: 355-61. 10.1159/000014179.CrossRefPubMed Rijtema M, Mosig D, Drukker A, Guignard JP: The effects of dimethyl sulfoxide on renal function of the newborn rabbit. Biol Neonate. 1999, 76: 355-61. 10.1159/000014179.CrossRefPubMed
30.
go back to reference Allen TM, Cullis PR: Drug delivery systems: entering the mainstream. Science. 2004, 19: 1818-22. 10.1126/science.1095833.CrossRef Allen TM, Cullis PR: Drug delivery systems: entering the mainstream. Science. 2004, 19: 1818-22. 10.1126/science.1095833.CrossRef
31.
go back to reference Batist G, Ramakrishnan G, Rao CS, Chandrasekharan A, Gutheil J, Guthrie T, Shah P, Khojasteh A, Nair MK, Hoelzer K, Tkaczuk K, Park , Lee LW: Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J Clin Oncol. 2001, 19: 1444-54.PubMed Batist G, Ramakrishnan G, Rao CS, Chandrasekharan A, Gutheil J, Guthrie T, Shah P, Khojasteh A, Nair MK, Hoelzer K, Tkaczuk K, Park , Lee LW: Reduced cardiotoxicity and preserved antitumor efficacy of liposome-encapsulated doxorubicin and cyclophosphamide compared with conventional doxorubicin and cyclophosphamide in a randomized, multicenter trial of metastatic breast cancer. J Clin Oncol. 2001, 19: 1444-54.PubMed
Metadata
Title
Improved therapeutic effectiveness by combining liposomal honokiol with cisplatin in lung cancer model
Authors
Qi-qi Jiang
Lin-yu Fan
Guang-li Yang
Wen-Hao Guo
Wen-li Hou
Li-juan Chen
Yu-quan Wei
Publication date
01-12-2008
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2008
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-8-242

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