General

Scientific Names: Gossypium herbaceum L.

Common Names:Cao Mian.

BOTANICAL:

来源: 为锦葵科植物草棉Gossypium herbaceum L.等的外果皮。

植物形态 : 一年生草本至亚灌木，高达1.5。疏被柔毛，叶互生；叶柄长2.5-8cm，被长柔毛；托叶线形，长5-10mm，早落；叶掌状5裂，直径5-10cm，通常宽超过于长，裂片宽卵形，深裂不到叶片的中部，先端短尖，基部心形，上面被星状长硬毛，下面被细绒毛，沿脉被长柔毛。花单生于叶腋，花梗长1-2cm，被长柔毛；小苞片基部合生，阔三角形，长2-3cm，宽超过于长，先端具6-8齿，沿脉被疏长毛；花萼杯状，5浅裂；花黄色，内面基部紫色，直径5-7cm。蒴果卵圆形，长约3cm，具喙，通常3-4室。种子大，大约1cm，分离，斜圆锥形，被白色长棉毛和短棉毛。花期7-9月。

Pharmacology

1. Wang X, et al., Bioactivities of gossypol, 6-methoxygossypol, and 6,6'-dimethoxygossypol. J Agric Food Chem . 2008 Jun 25; 56 ( 12 ): 4393-8 . Epub 2008 Jun 3.

化学成份 : 草棉根皮含棉酚（gossypol），黄酮（flavonoid），香草乙酮（acetovanillone），甜菜碱（betaine），甾醇（sterol），水杨酸（salicylic acid）等；根含皂甙（saponin），苯酚成分（phenol）。

Efficacy

棉酚 gossypol : 黄色粉末或结晶性粉末，无臭，无味。不溶于水，溶于甲醇、乙醇、乙醚、氯仿，易溶于石油醚。本品至少有三种消旋体结晶，熔点相应为184℃、199℃及214℃。

以二乙基亚硝胺(DEN)诱发大鼠实验性肝癌为模型,通过肝细胞光镜结构、超微结构;肝脏组织分化酶、增殖酶;肝细胞核内AgNORs计数;癌基因c-Myc及增殖细胞核抗原的表达等变化,探讨棉酚对大鼠实验性肝癌癌前病变的预防和治疗作用.结果:1.DEN诱癌过程中有癌基因c-Myc的参与;2.癌变过程中伴有与细胞增殖有关的酶活性增高和与细胞分化有关的酶活性降低;3.棉酚可能是通过直接作用于细胞器,抑制癌变细胞的细胞周期调控因子的表达,抑制rDNA的转录活性,以及抑制细胞增殖酶活性和增强细胞分化酶活性等多个环节来抑制细胞增殖,促进细胞分化,从而起到抗癌的作用.

近年来,多酚类药物的抗肿瘤作用日益受到重视。有研究表明,棉酚可能是一种颇有前途的抗癌药物。至今已有不少有关棉酚抗肿瘤作用的报道,其中涉及棉酚抗肿瘤的机制以及棉酚在体外培养的肿瘤细胞、动物模型和临床应用的研究较多。

In vitro:

1. Macoska JA, et, al, Gossypol promotes the apoptosis of bladder cancer cells in vitro. Pharmacol Res . 2008 Sep 16.
2. Sun J, et al., ApoG2 inhibits antiapoptotic Bcl-2 family proteins and induces mitochondria-dependent apoptosis in human lymphoma U937 cells. Anticancer Drugs . 2008 Nov; 19 ( 10 ): 967-74 .
3. Wei J, et al., Synthesis and evaluation of Apogossypol atropisomers as potential Bcl-x(L) antagonists. Cancer Lett . 2008 Sep 7.
4. Sun Y, et al., Apogossypolone, a nonpeptidic small molecule inhibitor targeting Bcl-2 family proteins, effectively inhibits growth of diffuse large cell lymphoma cells in vitro and in vivo. Cancer Biol Ther . 2008 Sep; 7 ( 9 ): 1418-26 . Epub 2008 Sep 4.
5. Etxebarria A, et al., Regulation of antiapoptotic MCL-1 function by gossypol: Mechanistic insights from in vitro reconstituted systems. Biochem Pharmacol . 2008 Aug 12.
6. Hu ZY, et al., ApoG2, a novel inhibitor of antiapoptotic Bcl-2 family proteins, induces apoptosis and suppresses tumor growth in nasopharyngeal carcinoma xenografts. Int J Cancer . 2008 Nov 15; 123 ( 10 ): 2418-29
7. Meng Y, et al., Natural BH3 mimetic (-)-gossypol chemosensitizes human prostate cancer via Bcl-xL inhibition accompanied by increase of Puma and Noxa. Mol Cancer Ther . 2008 Jul; 7 ( 7 ): 2192-202 .
8. Balakrishnan K, et al., Gossypol, a BH3 mimetic, induces apoptosis in chronic lymphocytic leukemia cells. Blood . 2008 Sep 1; 112 ( 5 ): 1971-80 . Epub 2008 Jun 19.
9. Boonsri S, et al., Cytotoxic and antibacterial sesquiterpenes from Thespesia populnea. J Nat Prod . 2008 Jul; 71 ( 7 ): 1173-7 . Epub 2008 Jun 14.
10. Wang L., et al., WL-276, an antagonist against Bcl-2 proteins, overcomes drug resistance and suppresses prostate tumor growth. Cancer Res . 2008 Jun 1; 68 ( 11 ): 4377-83 .
11. Kline MP, et al., R-(-)-gossypol (AT-101) activates programmed cell death in multiple myeloma cells. Exp Hematol . 2008 May; 36 ( 5 ): 568-76 . Epub 2008 Mar 17.
12. Boehm AL, et al., Combined targeting of epidermal growth factor receptor, signal transducer and activator of transcription-3, and Bcl-X(L) enhances antitumor effects in squamous cell carcinoma of the head and neck. Mol Pharmacol . 2008 Jun; 73 ( 6 ): 1632-42 . Epub 2008 Mar 6.
13. Moon DO, et al., Gossypol suppresses NF-kappaB activity and NF-kappaB-related gene expression in human leukemia U937 cells. Cancer Lett . 2008 Jun 18; 264 ( 2 ): 192-200 . Epub 2008 Mar 7.
14. Paoluzzi L, et al., Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma. Blood . 2008 Jun 1; 111 ( 11 ): 5350-8 . Epub 2008 Feb 21.
15. Amold AA, et al., Preclinical studies of Apogossypolone: a new nonpeptidic pan small-molecule inhibitor of Bcl-2, Bcl-XL and Mcl-1 proteins in Follicular Small Cleaved Cell Lymphoma model. Mol Cancer . 2008 Feb 14; 7 : 20 .
16. Rodríguez-Enríquez S, et al., Energy metabolism transition in multi-cellular human tumor spheroids. J Cell Physiol . 2008 Jul; 216 ( 1 ): 189-97 .
17. Brozic P, et al., Inhibitors of 17beta-hydroxysteroid dehydrogenase type 1. Curr Med Chem . 2008; 15 ( 2 ): 137-50 . Review.
18. Kitada S, et al., Bcl-2 antagonist apogossypol (NSC736630) displays single-agent activity in Bcl-2-transgenic mice and has superior efficacy with less toxicity compared with gossypol (NSC19048). Blood . 2008 Mar 15; 111 ( 6 ): 3211-9 . Epub 2008 Jan 17.
19. Loberg RD, et al., In vivo evaluation of AT-101 (R-(-)-gossypol acetic acid) in androgen-independent growth of VCaP prostate cancer cells in combination with surgical castration. Neoplasia . 2007 Dec; 9 ( 12 ): 1030-7 .
20. Li ZM, et al., Synergistic cytotoxicity of Bcl-xL inhibitor, gossypol and chemotherapeutic agents in non-Hodgkin's lymphoma cells. Cancer Biol Ther . 2008 Jan; 7 ( 1 ): 51-60 . Epub 2007 Oct 8.
21. Meng Y, et al., (-)Gossypol and its combination with imatinib induce apoptosis in human chronic myeloid leukemic cells. Leuk Lymphoma . 2007 Nov; 48 ( 11 ): 2204-12 .
22. Schwartz PS, et al., 2-Methoxy antimycin reveals a unique mechanism for Bcl-x(L) inhibition. Mol Cancer Ther . 2007 Jul; 6 ( 7 ): 2073-80 .
23. Ko CH, et al., Gossypol reduction of tumor growth through ROS-dependent mitochondria pathway in human colorectal carcinoma cells. Int J Cancer . 2007 Oct 15; 121 ( 8 ): 1670-9 .
24. Wolter KG, et al., Therapeutic window for melanoma treatment provided by selective effects of the proteasome on Bcl-2 proteins. Cell Death Differ . 2007 Sep; 14 ( 9 ): 1605-16 . Epub 2007 Jun 1.
25. Kasten-Pisula U , et al., Radiosensitization of tumour cell lines by the polyphenol Gossypol results from depressed double-strand break repair and not from enhanced apoptosis. Radiother Oncol . 2007 Jun; 83 ( 3 ): 296-303 . Epub 2007 May 22.
26. Badawy SZ, et al., Gossypol inhibits proliferation of endometrioma cells in culture. Asian J Androl . 2007 May; 9 ( 3 ): 388-93 .
27. Mohammad RM , et al., Preclinical studies of TW-37, a new nonpeptidic small-molecule inhibitor of Bcl-2, in diffuse large cell lymphoma xenograft model reveal drug action on both Bcl-2 and Mcl-1. Clin Cancer Res . 2007 Apr 1; 13 ( 7 ): 2226-35 .
28. Jia L., et al., Comparison of pharmacokinetic and metabolic profiling among gossypol, apogossypol and apogossypol hexaacetate. Cancer Chemother Pharmacol . 2008 Jan; 61 ( 1 ): 63-73 . Epub 2007 Mar 14.
29. Ye W, et al., Modulation of multidrug resistance gene expression in human breast cancer cells by (-)-gossypol-enriched cottonseed oil. Anticancer Res . 2007 Jan-Feb; 27 ( 1A ): 107-16 .
30. Zhang M, et al., Differential growth inhibition and induction of apoptosis by gossypol between HCT116 and HCT116/Bax(-/-) colorectal cancer cells. Clin Exp Pharmacol Physiol . 2007 Mar; 34 ( 3 ): 230-7 .
31. Zhang M, et al., Gossypol induces apoptosis in human PC-3 prostate cancer cells by modulating caspase-dependent and caspase-independent cell death pathways. Life Sci . 2007 Jan 30; 80 ( 8 ): 767-74 . Epub 2006 Nov 10.
32. Yeow WS, et al., Gossypol, a phytochemical with BH3-mimetic property, sensitizes cultured thoracic cancer cells to Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand. J Thorac Cardiovasc Surg . 2006 Dec; 132 ( 6 ): 1356-62 . Epub 2006 Oct 30.
33. Song JJ, et al., Evidence for two modes of development of acquired tumor necrosis factor-related apoptosis-inducing ligand resistance. Involvement of Bcl-xL. J Biol Chem . 2007 Jan 5; 282 ( 1 ): 319-28 . Epub 2006 Nov 15.
34. Huang YW, et al., Effects of serum on (-)-gossypol-suppressed growth in human prostate cancer cells. Anticancer Res . 2006 Sep-Oct; 26 ( 5A ): 3613-20 .
35. Wang G, et al., Structure-based design of potent small-molecule inhibitors of anti-apoptotic Bcl-2 proteins. J Med Chem . 2006 Oct 19; 49 ( 21 ): 6139-42 .
36. Lei X, et al., Gossypol induces Bax/Bak-independent activation of apoptosis and cytochrome c release via a conformational change in Bcl-2. FASEB J . 2006 Oct; 20 ( 12 ): 2147-9 . Epub 2006 Aug 25.
37. Cleverley J, et al., American Society of Clinical Oncology--42nd annual meeting. Poster presentations on leukemia and cytotoxic chemotherapy. 2-6 June 2006, Atlanta, GA, USA. IDrugs . 2006 Aug; 9 ( 8 ): 520-2 .

In vivo:

1. Sun Y, et al., Apogossypolone, a nonpeptidic small molecule inhibitor targeting Bcl-2 family proteins, effectively inhibits growth of diffuse large cell lymphoma cells in vitro and in vivo. Cancer Biol Ther . 2008 Sep; 7 ( 9 ): 1418-26 . Epub 2008 Sep 4.
2. Paoluzzi L, et al., Targeting Bcl-2 family members with the BH3 mimetic AT-101 markedly enhances the therapeutic effects of chemotherapeutic agents in in vitro and in vivo models of B-cell lymphoma. Blood . 2008 Jun 1; 111 ( 11 ): 5350-8 . Epub 2008 Feb 21.
3. Loberg RD, et al., In vivo evaluation of AT-101 (R-(-)-gossypol acetic acid) in androgen-independent growth of VCaP prostate cancer cells in combination with surgical castration. Neoplasia . 2007 Dec; 9 ( 12 ): 1030-7 .

Clinical:

1. Johnson PW, et al., New targets for lymphoma treatment. Ann Oncol . 2008 Jun; 19 Suppl 4 : iv56-9 . Review.
2. Politzer WM, et al., Long-term clinical remission of a patient with chronic lymphocytic leukemia using alternative treatment option: cottonseed oil (gossypol). Phytomedicine . 2008 Aug; 15 ( 8 ): 563-5 . Epub 2008 Jun 24.

Safety

用药禁忌: 。