Kalopanaxsaponin A Inhibits the Invasion of Human Oral Squamous Cell Carcinoma by Reducing Metalloproteinase-9 mRNA Stability and Protein Trafficking

Abstract

Key words Kalopanaxsaponin-A; oral cancer; anti-invasive effect; metalloproteinase-9; HuR; Ras-associated binding 1AOral squamous cell carcinoma (OSCC) is a common malignant tumor in the oral and maxillofacial region, and it is the sixth most common cancer worldwide. In high-risk countries such as Sri Lanka, India, Pakistan, and Bangladesh, oral cancer may contribute up to 25% of all new cases of cancer, and in most countries, the five-year survival rates for cancers of the tongue, oral cavity and oropharynx are around 50%. 1)OSCC is characterized by a high degree of local invasiveness and a high rate of metastasis to the cervical lymph nodes. 2)Despite multidisciplinary treatment with surgery, chemotherapy and radiation, the overall survival rate has not improved significantly in patients with oral cancer. In addition, many patients who are successfully treated for oral cancer have to cope with devastating consequences in their appearance and function, including eating, drinking, swallowing and speaking.1) Consequently, controlling the invasiveness and metastasis of oral cancer represents an important therapeutic goal.OSCC progression is frequently associated with the acquisition of a more invasive phenotype and with proteinasedependent extracellular matrix (ECM) degradation.2) Invasive OSCC cells secrete matrix metalloproteinases (MMPs), which are mainly responsible for the degradation of environmental barriers such as ECM and the basement membrane. 3,4)

Overexpression of Rab1B and MMP9 predicts poor survival and good response to chemotherapy in patients with colorectal cancer

“…In CRC, previous studies indicate that the expression of MMP9 is associated with metastasis [18-20] and poor prognosis [21-23]. Interestingly, a recent study showed that Rab1A knockdown decreases MMP9 expression and inhibites MMP9-mediated invasiveness of human oral squamous cell cancer cells, suggesting that Rab1A regulates MMP9-mediated invasiveness [24]. Given the high homology between Rab1A and Rab1B, it would be interesting to determine whether Rab1B protein promotes invasiveness and metastasis by upregulating the expression of MMP9 in CRC.…”

Hexane and Chloroform Fractions of Laetiporus sulphrueus var. miniatus Inhibit Thrombin-treated Matrix Metalloproteinase- 2/9 Expression in Human Oral Squamous Carcinoma YD-10B Cells

“…PMA is widely used as a tumor promoter for the stimulation of cell invasion in various types of cancer cells [36][37][38]. In PMA-treated YD-10B cells, mRNA expression and protein activation of MMP-2/-9 were highly inhibited in the hexane and chloroform fractions (Fig.…”

Nucleolin mediated pro‐angiogenic role of Hydroxysafflor Yellow A in ischaemic cardiac dysfunction: Post‐transcriptional regulation of VEGF‐A and MMP‐9

“…Besides the transcriptional regulation, mRNA stability also regulated the protein expressions of VEGF‐A and MMP‐9 42, 43, 44, 45. Carraway KR et al.…”

“…demonstrated that CIL‐102 reduced MMP‐9 expression and invasion and migration of K562 cells through simultaneous suppression of MMP‐9 genetic transcription and mRNA stability 44. Hwang et al45 proved that Kalopanaxsaponin A inhibited the invasiveness of oral cancer by reducing MMP‐9 mRNA stability and expression. The present study demonstrated that overexpression of nucleolin enhanced that stability of VEGF‐A and MMP‐9 mRNA, vice versa.…”