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Induction of Apoptotic Cell Death and in Vivo Growth Inhibition of Human Cancer Cells by a Saturated Branched-Chain Fatty Acid, 13-Methyltetradecanoic Acid¹

Pentagenic Pharmaceuticals, Inc., Diamond Bar, California 91765 [Z. Y., S. L., X. C., H. C., M. H.], and the Department of Pathology, University of Southern California School of Medicine, Los Angeles, California 90033 [J. Z.]

A saturated branched-chain fatty acid, 13-methyltetradecanoic acid (13-MTD), was purified from a soy fermentation product, which was used by many cancer patients as a treatment supplement. Our preliminary study indicated that 13-MTD could induce cell death in human cancer cell lines K-562, MCF7, DU 145, NCI-SNU-1, SNU-423, NCI-H1688, BxPC3, and HCT 116. The ID₅₀ dosage of 13-MTD for these tumor cells ranged from 10 to 25 µg/ml. Further investigation revealed that 13-MTD caused tumor cell death through rapid induction of apoptosis, which could be detected 2 h after the treatment of tumor cells with 13-MTD. Xenograft tumors of prostate carcinoma cell line DU 145 and hepatocarcinoma LCI-D35 were orthotopically implanted into nude mouse prostate and liver, respectively. 13-MTD was administered p.o. once daily to the implanted mice for 40 days. Our results showed that 13-MTD could effectively inhibit the growth of orthotopic tumor implants of both cell lines compared with control groups. The average inhibition rate was 84.6% for DU 145 and 65.2% for LCI-D35 (P < 0.01). LD₅₀ test results showed that mice could well sustain the oral feeding of 5 g/kg/day without observable anomaly. Our preliminary data demonstrated that 13-MTD could effectively inhibit in vitro and in vivo growth of various cancer cell lines by inducing apoptosis without significant toxic side effects, suggesting 13-MTD as a potential candidate for chemotherapy of human cancers.

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