Tanshinone IIA inhibits cell viability and promotes PUMA-mediated apoptosis of oral squamous cell carcinoma

Shuangze Han; Xinfang Yu; Ruirui Wang; Xiaocong Wang; LuLu Liu; Qing Zhao; RongBo Xie; Ming Li; Zhong Su Zhou

doi:10.7150/jca.84537

Tanshinone IIA inhibits cell viability and promotes PUMA-mediated apoptosis of oral squamous cell carcinoma

J Cancer. 2023 Aug 6;14(13):2481-2490. doi: 10.7150/jca.84537. eCollection 2023.

Authors

Shuangze Han^{1

2}, Xinfang Yu³, Ruirui Wang⁴, Xiaocong Wang^{5

6}, LuLu Liu^{5

6}, Qing Zhao^{5

6}, RongBo Xie^{5

6}, Ming Li^{5

6}, Zhong Su Zhou¹

Affiliations

¹ The Third Hospital of Changsha, Changsha 410015 Hunan, People's Republic of China.
² Department of Ultrasound, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
³ Department of Medicine, Baylor College of Medicine, Houston, TX, 77054, USA.
⁴ Department of Radiology, the Third Xiangya Hospital, Changsha, 410013, China.
⁵ Hunan University of Chinese Medicine Affiliated Stomatological Hospital, Changsha 410208 Hunan, People's Republic of China.
⁶ Changsha Stomatological Hospital, Changsha 410004 Hunan, People's Republic of China.

Abstract

Apoptosis alteration is responsible for tumorigenesis and tumor resistance to therapies. The natural product Tanshinone IIA (Tan IIA) exhibits potent inhibitory effects against various tumors. However, the effect of Tan IIA on apoptosis and its underlying mechanism remains elusive in oral squamous cell carcinoma (OSCC). Here, we demonstrated that Tan IIA dose-dependently suppressed cell viability and colony formation in CAL27, SCC4, and SCC25 cells. Moreover, Tan IIA inhibited Akt activation from inducing Foxo3a dephosphorylation and PUMA-mediated apoptosis. PUMA or Foxo3a knockdown compromised the inhibitory effect of Tan IIA on OSCC cells. Tan IIA administration inhibited CAL27-deprived xenograft tumor growth and increased PUMA expression in vivo. Tan IIA synergistically intensified the efficacy of CDDP/5-FU-based chemotherapy on OSCC cells. Overall, our results revealed that Tan IIA exerted potent antitumor effects via promoting PUMA-mediated apoptosis in OSCC cells.

Keywords: PUMA; Tanshinone IIA; oral squamous cell carcinoma.