Elucidation of Callistemon lanceolatus-derived natural compounds in STAT 3 pathway against human cancer cells: In silico and in vitro studies

Mubashir Zafar ¹ Sadaf Anwar ¹ Malik Asif Hussain ¹ Naved Iqbal ² Abrar Ali ¹ Sadaf . ³ Mohammad Zeeshan Najm ⁴ Mohd Adnan Kausar ^1,2*

• ¹ College of Medicine, University of Hail, Hail, Saudi Arabia
• ² University of Hail, Ha'il, Saudi Arabia
• ³ Jamia Millia Islamia, New Delhi, National Capital Territory of Delhi, India
• ⁴ Apeejay Stya University, Gurgaon, Haryana, India

Many human tumours have hyperactive signal transducer and activator of transcription 3 (STAT3, positioning it as a prime target for natural compounds with anticancer properties. This study investigated three small-molecule STAT3 inhibitors derived from Callistemon lanceolatus: cyanidin-3,5-diglucoside, kaempferol-3-o-β-d-galactopyranoside, and quercetin-3-o-(2"-o-galloyl)-β-d-galactopyranoside. These compounds were explored through virtual screening and molecular dynamics (MD) simulations to understand the intracellular processing of activated STAT3. The biological effects of these STAT3 inhibitors on human cancer cells were assessed via simulation, revealing that the active components in these compounds inhibited cancer cell migration and invasion and suppressed the proliferation of noncancer cells. Moreover, these natural compounds from C. lanceolatus downregulated the expression of STAT3 downstream target proteins, indicating their potential as therapeutic agents against cancer. Thus, cyanidin-3,5-diglucoside, kaempferol-3-o-β-d-galactopyranoside, and quercetin-3-o-(2"-o-galloyl)-β-d-galactopyranoside from C. lanceolatus are promising candidates for cancer treatment.