Page 198 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-16

Bioactive cembranoid diterpene, sarcophytol A, from Sarcophyton species:

Structural characterization and therapeutic potential

1,2
3
4
Szu-Hsiang Tsai, #,1,7 Tsen-Ni Tsai, Y u -Ming Hsu, Ken-Ming Chang, Shang-Yi Tu, 5,6,7
Mei-Chin Lu* ,1,6,7

1 Graduate Institute of Marine Biology, National Dong Hwa University, Pingtung, Taiwan
2 Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Medical
University Hospital, Kaohsiung, Taiwan
3 Research Center for Precision Environmental Medicine, Kaohsiung Medical University,
Kaohsiung, Taiwan
4 Department of Pharmacy and Master Program, Tajen University, Pingtung, Taiwan
5 Department of Marine Biotechnology and Resources, National Sun Yat-sen University,
Kaohsiung, Taiwan
6 Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
7 National Museum of Marine Biology and Aquarium, Pingtung, Taiwan
* E-mail: jinx6609@nmmba.gov.tw (M.-C. L.)

Abstract
Sarcophytol A, a major bioactive compound isolated from Sarcophyton species, has been
shown to exert potent anti-tumor activity. In this study, we investigated the cytotoxic effects of
sarcophytol A on a T-cell acute lymphoblastic leukemia (T-ALL) cell line (CCRF) and a
lymphoma cell line (U937). MTT assays revealed dose-dependent cytotoxicity, with IC₅₀ values
of 8.76 µg/mL and 10.62 µg/mL, respectively, after 72 hours of treatment. To further elucidate
the underlying mechanisms of sarcophytol A-induced cytotoxicity, we conducted a series of
flow cytometric analyses, including Annexin V/PI staining, JC-1 assay, MitoSOX, and Fluo-3
calcium assays. Western blotting was performed to evaluate the expression of apoptosis- and
stress-related proteins. The results demonstrated that sarcophytol A significantly induced
apoptosis, as evidenced by increased levels of cleaved caspase-3 and cleaved PARP, along with
elevated proportions of both early and late apoptotic cells. Notably, cleaved caspase-8, a key
initiator of the extrinsic apoptosis pathway, remained unchanged, suggesting that apoptosis was
primarily mediated via the intrinsic mitochondrial pathway. JC-1 and MitoSOX assays
confirmed a loss of mitochondrial membrane potential and an increase in mitochondrial
superoxide production. Furthermore, Fluo-3 analysis revealed intracellular calcium
accumulation following sarcophytol A treatment. Western blot analysis showed upregulation of
ER stress markers, including Ero1-Lα, IRE1α, calnexin, and PDI, indicating activation of
endoplasmic reticulum stress pathways. Additionally, a cell-free tubulin polymerization assay
demonstrated that sarcophytol A promotes microtubule polymerization, suggesting interference
with cytoskeletal dynamics as part of its anti-cancer mechanism. In conclusion, sarcophytol A
induces apoptosis in T-ALL and lymphoma cell lines through a multifaceted mechanism
involving mitochondrial dysfunction, ROS generation, calcium overload, ER stress activation,
and enhanced tubulin polymerization. These findings suggest that sarcophytol A is a promising
candidate for the development of novel therapeutic strategies against hematological
malignancies.

Keywords: Anticancer; Apoptosis; Leukemia; Marine drug; Tubulin polymerization