Table 2 Phytochemicals in the treatment of Pancreatic cancer: Table shows a variety of phytochemicals used in the treatment of pancreatic cancer. It also lists out their IC₅₀ values in the anticancer activity against pancreatic cancer. Simultaneously the table shows details of the model on which the study was carried on

1.

Alkaloid

Ancistrolikokine E₃

Ancistrocladus likoko

-

Invitro

PANC-1

Inhibition of Akt/mTOR signaling pathway along with inhibition of autophagy at an early stage in the nutrient-deprived medium

2.5μM

[75]

2.

Sanguinarine

Sanguinaria canadensis

-

Invitro

AsPC-1, PANC-1, and HPNE; cancer stem cells; 3D spheroids

Induction of oxidative stress and inhibition of Sonic hedgehog- Gli- Nanog pathway

-

[76]

3.

Alkaloid toxin

Aconitine

Aconitum

-

Invitro and Invivo

Mia-PaCa-2 and PANC-1;

Male athymic nude mice

Reduction of NFκB leading to increase in cell apoptosis

20-40μM

[77]

4.

Biomolecule

Sporamin

Ipomoea batatas

-

Invitro

PANC-1 and BxPC-3

Downregulation of NFκB pathway and induction of apoptosis

-

[78]

5.

Bisbenzylisoquinoline alkaloid

Tetrandrine

Cyclea peltata

-

In vitro

PANC-1

Increase in ROS, caspase 8, caspase 9, and caspase 3 leading to activation of apoptosis

51–54μM (24 h) and 22–27μM (48 h)

[79]

6.

Bis Benzyl Tetrahydroisoquinoline

Alkaloid

Fangchinoline

Stephania tetrandra

-

In vitro

Mia-PaCa-2 and PANC-1

Growth inhibition and apoptosis by inactivation of nuclear receptor NR4A1

11.1μM and 17μM

[80]

7.

Diterpene

Sugiol

-

-

In vitro

Mia-PaCa-2

Induction of ROS mediated damage to mitochondrial membrane potential, mitochondrial apoptosis, and cell cycle arrest

15μM

[81]

8.

Isothiocyanate

Erucin

Eruca sativa

-

In vitro

AsPC-1

Inhibition of ERK1/2 phosphorylation; altered cell cycle and reduction in cell migration and caused proapoptotic effects

-

[82]

9.

Limonoid

Nimbolide

Azadirachta indica

-

In vitro and in vivo

HPAC, PANC-1, Mia-PaCa-2, HPNE; Athymic nude mice

Inhibition of proliferation and metastasis via increase in ROS generation that causes mitochondria-mediated apoptosis

3–5μM

[83]

10.

Monoterpene glycoside

Paeoniflorin

Paeonia lactiflora

-

In vitro

Capan-1 and Mia-PaCa-2

Upregulation of HTRA3 expression and enhancement of apoptosis

862.7μM and 489.5μM

[84]

11.

Phenanthrenequinone

Tanshinone-IIA

Salvia miltiorrhiza

Corn oil

In vivo

Male nude SCID mice implanted with BxPC-3 cells

Inducing endoplasmic reticulum stress by increasing level of PERK, ATF6, Caspase12, IRE1α, eIF2α, pJNK, CHOP, and Caspase3 proteins

-

[85]

12.

Polyphenol

Curcumin

Curcuma longa

DMSO

In vitro

Patu 8988t and PANC-1

Induction of apoptosis and cell cycle arrest; suppression of cell growth, cell migration, and invasion which was mechanistically due to downregulation of Cdc20 oncoprotein

-

[86]

13.

Ellagic acid

Pomegranate and strawberries

-

In vitro and in vivo

PANC-1;

BALB/c nude mice

Inhibition of expression of COX2, NFκB and vimentin along with increased expression of E-Cadherin and cell cycle arrest which causes inhibition of cell invasion and migration, cell growth, and repair

7.38μg/ml (24h), 6.42μg/ml (48h), 5.41μg/ml (72h)

[87]

14.

Epigallocatechin 3 gallate

Green tea

-

In vitro and in vivo

PANC-1, Mia-PaCa-2, BxPC-3, HPAF-II, CFPAC1, Su.86.86, HPNE and FC1245; C57BL/6J mice

Inhibition of cell migration and invasion partly via inhibition of Akt signaling pathway and epithelial to mesenchymal transition

-

[88]

15.

Sesquiterpene

Elemene

Zingiberaceae plants

-

In vitro and in vivo

BxPC-3 and PANC-1; Female BALB/c nude mice

Regulation of p53 and Bcl-2 proteins

-

[89]

16.

Matricine

Matricaria chamomilla

-

In vitro

Capan-2 and hTERT-HPNE

Activated apoptosis and inhibited invasion and migration via PI₃K/Akt/mTOR pathway

20μM and 80μM

[90]

17.

Steroidal glycoside

Degalactotigonin

Solanum nigrum

-

In vitro

PANC-1 and Mia-PaCa-2

Cell cycle arrest through inhibition of EGFR signaling pathway and inducing apoptosis

2.9± 0.2μM and 6.4± 0.4μM

[91]

18.

Triterpenoid

Aphanin

Amoora rohituka

-

In vitro

HPAF-II, HPAC, BxPC-3 and hTERT-HPNE

G₀-G₁ cell cycle arrest, inhibition of K-Ras G12D mutant activity via reduction in expression of STAT3, pSTAT3, Akt, pAkt, cyclin-D1, and c-Myc and induction of apoptosis

12.80μM, 17.26μM, 15.68μM and 46.99μM

[92]

19.

Toosendanin

Melia toosendan

-

In vitro and in vivo

PANC-1 and AsPC-1; BALB/c mice

Inhibition of epithelial to mesenchymal transition by downregulation of PI₃K/Akt/mTOR signaling pathway

-

[93]

20.

Tetranortriterpenoid

Gedunin

Azadirachta indica

-

Invitro and Invivo

HPAC, PANC-1, Mia-PaCa-2 and HPNE; Female athymic nude mice

Induction of intrinsic and extrinsic apoptotic pathways and inhibition of sonic hedgehog pathways

25μM

[94]